Tau RT-QuIC: Ultrasensitive Assays for the Detection of Tau Seeding Activity Associated with Tauopathies


Tauopathies are a category of neurodegenerative diseases defined by the abnormal accumulation of misfolded tau protein aggregates (often in the form of amyloid filaments) within the brain. Tau proteins exist in six isoforms, three of which contain three microtubule binding regions (3R), and the remainder contain four microtubule binding regions (4R). Tauopathies are characterized, in part, based on the ratio of 3R/4R misfolded tau proteins that make up the aggregates. This technology enables rapid, ultrasensitive and economical differentiation of self-propagating tau aggregates associated with tauopathies in crude biospecimens. The assays use recombinant, truncated 3R, 4R, or 3R+4R tau protein substrates as indicators of tau aggregates. Specifically, misfolded tau aggregates (contained in a biological sample) seed the polymerization of either 3R, 4R, or 3R+4R tau substrates, and the polymers (amyloid fibrils) are detected as an amplified indicator of even extremely low concentrations of tau aggregates within the biological sample and aid in identification of the tauopathy. In its current embodiment, this assay has been used to detect tau seeds in brain tissue from patients with Alzheimer’s disease, Pick disease, chronic traumatic encephalopathy, corticobasal degeneration, progressive supranuclear palsy, certain frontotemporal dementias, and other tauopathies. For several of these diseases, tau RT-QuIC assays have also detected tau seeding activity in patients’ cerebrospinal fluid.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404.

Potential Commercial Applications: Competitive Advantages:
  • Diagnosis of tauopathies, including: Alzheimer’s disease, Pick disease, corticobasal degeneration, chronic traumatic encephalopathy, progressive supranuclear palsy, and frontotemporal dementias with tau deposition.
  • Measurement of levels of pathological tau aggregates in biospecimens.
  • Analysis of tauopathy-associated disease progression
  • Clinical trial / drug development companion diagnostic
 
  • Uses a consistent, concentrated source of truncated tau protein
  • Rapid and economical
  • Highly sensitive and specific


Inventors:

Byron Caughey (NIAID)  ➽ more inventions...

Eri Saijo (NIAID)  ➽ more inventions...

Allison Kraus (NIAID)  ➽ more inventions...

Michael Metrick (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 16/474,040
PCT Application No. PCT/US2017/069024
US Application No. 62/440,885

Publications:
Saijo, Eri et al. “Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid”. Acta Neuropathologica vol. 133 (2017):751-765. PMID 28293793
Kraus, Allison et al. “Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease”. Acta Neuropathologica vol. 137, 4 (2019): 585-598. PMID 30570675
Metrick II Michael et al., “Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons”. Proc Natl Acad Sci USA vol. 116, 46 (2019):23029-23039. PMID 31641070
Saijo, Eri et al. “4-repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration”. Acta Neuropathologica vol 139, 4(2020):63-77. PMID 31616982
Correction to: Saijo, Eri et al. “4-repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration”. Acta Neuropathologica vol 139, 4(2020):63-77. PMID 31748840
Metrick II, Michael et al. “A single ultrasensitive assay for detection and discrimination of tau aggregates of Alzheimer and Pick diseases”. Acta Neuropathologica Communications vol. 8, 1 (2020):22. 32087764

Collaboration Opportunity:

To license this technology, please contact Jeffrey Thruston at 301-594-5179 or jeffrey.thruston@nih.gov, and reference E-015-2017-0.


Licensing Contact:
Jeffrey Thruston,
Email: jeffrey.thruston@nih.gov
Phone: 301-594-5179

OTT Reference No: E-015-2017-0
Updated: Oct 14, 2020